The objective of the proposed project is to study the neurochemical nature of the retinal ganglion cell (RGC) projection to the hypothalamic suprachiasmatic nucleus (SCN) and to explore the anatomical and chemical basis for its regulation of circadian physiological and biochemical parameters. Serotonergic and catecholaminergic SCN input has been reported, as well as the presence of other putative neurotransmitter substances, taurine, GABA, glumatiacid, glycine, acetylcholine and peptides. These substances or their related enzymes will be measured in the SCN and other CNS nuclei removed by microdissection, using sensitive and specific radioisotopic or HPLC techniques. The circadian pattern of rectal temperature and motor activity will be correlated with the possible temporal changes in biochemical parameter in entrained animals sacrificed at six-hour intervals during the 24-hour period. The influence of nuronal input into the SCN will be examined in two types of experiments. Once the presence of substances and temporal fluctuations are established, selective lesion of projections to the SCN will be made, including the ventral lateral geniculate nucleus (LGN), dorsal and median raphe, as well as orbital enucleation. Of interest will be the effect of enucleation on SCN and dorsal LGN taurine, since each receive projections from RGC. The effect of these lesions on circadian rhythmic phenomena (temperatre, activity, pineal function) will be evaluated. To probe the importance of light as a stimulus to the synchronization of the circadian parameters and the placticity of this system, animals entrained to a 12:12 light-dark cycle will be exposed to constant ligt, constant dark or 6:18 light-dark cycles and circadian physiological and biochemical parameters measured. The experiments outlined should contribute to the understanding of the chemical nature of components of the visual system, how visual information influences the SCN and how they both participate in the regulation of cyclic physiological and neurochemical phenomena.